Interleukin-2 therapy after bone marrow or stem cell transplantation for hematologic malignancies.
OBJECTIVE
Autologous or allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT) for advanced hematologic malignancies is associated with a high relapse rate. It has been postulated that recombinant interleukin-2 (rIL-2) administered as consolidative immunotherapy early after BMT or SCT, at a time of minimal residual disease, might reduce the relapse rate. We review here preliminary results from a series of studies designed to investigate the safety, immunomodulatory effects, and clinical benefits of rIL-2 therapy following autologous and allogeneic BMT and SCT.


METHODS
Patients with hematologic malignancies underwent autologous or allogeneic BMT or SCT and received rIL-2 by continuous intravenous infusion a median of 33 to 56 days later. In all trials, the rIL-2 regimen consisted of a moderate induction dose for 4 to 5 days in the hospital, 4 to 6 days of rest, and a low maintenance dose for 10 days in the outpatient setting. A phase I trial of Roche rIL-2 after autoBMT, a feasibility trial of autologous lymphokine-activated killer cells with rIL-2, and another phase I/II trial of Chiron rIL-2 after autoBMT were performed. A similar phase I trial of IL-2 after alloBMT was also performed in children with acute leukemia beyond first complete remission.


RESULTS
An rIL-2 regimen has been identified that can be tolerated early after transplantation. Administration of this rIL-2 regimen induces marked increases in CD3+CD8+ T lymphocytes and CD3-CD56+ natural killer cells and enhances their antitumor cytolytic activity. Encouraging but somewhat inconsistent clinical outcomes were noted in phase I/II trials in patients with lymphoma and acute myeloid leukemia.


CONCLUSIONS
The results of phase I/II trials are sufficiently encouraging to justify prospectively randomized phase III trials to determine whether rIL-2 after autologous SCT will reduce the rate of posttransplantation relapse and improve survival in patients with advanced hematologic malignancies.
Fefer
A
A
University of Washington School of Medicine, Division of Medical Oncology, USA.
Robinson
N
N
Benyunes
M C
MC
Bensinger
W I
WI
Press
O
O
Thompson
J A
JA
Lindgren
C
C
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007167:Immunotherapy; D007223:Infant; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
D007376:Interleukin-2; D011994:Recombinant Proteins